Circulating Forms of Insulin-like Growth Factor-I (IGF-I) /Somatomedin C (SMC) in Fetal Life

Abstract

IGF-I/SMC shows mitogenic activities in a wide variety of cell types and stimulates cell growth in vitro and in vivo. Unlike most other peptide hormones, IGF-I/SMC circulates in the plasma as macromolecular complexes with specific plasma binding proteins, approximate molecular weight of 150K and 40K daltons. In order to elucidate the roles of IGF-I/SMC for fetal and postnatal development, the levels of plasma IGF-I/SMC, distribution of circulating IGF-I/SMC on its binding proteins, and profiles of unsaturated somatomedin binding proteins (USBP) were estimated in newborns and a growth-retarded infant (leprechaunism). The concentrations of IGF-I/SMC in cord plasma increased gradually after the 28th week of gestation and reached 37.3 +/- 14.6 ng/ml (Mean +/- S.D.) in full term infants. Although the levels of IGF-I/SMC in cord plasma were significantly lower than those in non-pregnant women (188 +/- 58), they showed a positive correlation with birth weight and relative birth weight (R.B.W.: percentage comparison to the average birth weight of normal infants in the same gestational week). In adult plasma, immunoreactive IGF-I/SMC was eluted predominantly in 150K dalton region (73.5%) and to a lesser extent (26.5%) in 40K dalton, and two apparent peaks of USBP could also be determined in both 150K and 40K dalton regions. On the other hand, in fetal plasma 84.4% of immunoreactive IGF-I/SMC was eluted in 40K region on the 20th week, but on the 26th week, 71.6% of IGF-I/SMC was eluted in 150K region and after the 35th week, more than 70% of IGF-I/SMC was determined in 150K region as observed in adult plasma. However, 150K.USBP could not be detected in cord plasma obtained from appropriate-for-date(AFD) infants until after the 35th week of gestation. Additionally, a positive correlation was demonstrated between 150K.USBP/40K.USBP ratio and birth weight. Some cases of small-for-date(SFD) infants whose IGF-I/SMC circulated mainly as 150K complex could catch up on their growth early in postnatal life. However, in the SFD newborns, if either 150K.USBP or 150Kcomplex of IGF-I/SMC could not be detected, their growth spurt was remarkably delayed until a year after birth. Furthermore, the similar disorders of IGF-I/SMC distribution and its USBP profile were also observed in the case of leprechaunism, who showed severe intrauterine and postnatal growth retardation.(ABSTRACT TRUNCATED AT 400 WORDS)